This invention relates to instruments and techniques for thermally-mediated therapies of targeted tissue volumes in a patient""s LES (lower esophageal sphincter) to treat gastro-esophageal reflux disease (GERD) in a minimally invasive manner. The thermally-mediated treatment, in a low temperature range, selectively injures cells and proteins within the (LES) to induce a predictable wound healing response to populate the targeted tissue with collagen matrices as a means of altering the bio-mechanical characteristics of the LES. In a slightly higher temperature range, an alternative thermally-mediated treatment is used to shrink native collagen fibers within the LES to xe2x80x9cmodelxe2x80x9d the dimensions and laxity of the LES. The novel treatment techniques are preferably performed with a trans-esophageally introduced bougie-type instrument and are adapted to take the place of more invasive surgical methods for treating GERD (e.g., Nissen fundoplications) in the treatment of the less severe GERD cases.
Gastro-esophageal reflux disease (GERD) is a digestive disorder caused by dysfunction in a patient""s lower esophageal sphincter (LES). In normal swallowing, the LES progressively opens to allow food to pass into the stomach and thereafter tightens to prevent food and stomach acids from flowing back into the esophagus. Gastro-esophageal reflux occurs when the stomach""s contents flow upwardly into the esophagus. Typically, such acid reflux results from anatomic abnormalities in the LES and surrounding structures, such as overly relaxed muscle tone within the LES, a shortened esophageal length within the abdominal cavity, insufficient intra-abdominal pressures, and/or from a contributory factor such as a hiatal hernia.
Prolonged acid reflux can cause serious complications such as esophagitis, erosions, esophageal bleeding or ulcers. In addition, chronic scarring caused by acid reflux can cause a narrowing or stricture in the esophagus. Some patients develop Barrett""s esophagus which is a form of severe damage to the esophageal lining. It is believed that Barrett""s esophagus is a precursor to esophageal cancer.
As many as 20 million American adults suffer from moderate to severe GERD. For chronic GERD and heartburn, a physician may prescribe medications to reduce acid in the stomach, such as H2-blockers (cimetidine, famotidine, nizatidine and ranitidine). Another form of drug therapy utilizes a proton pump inhibitor (PPI) that inhibits an enzyme in the acid-producing cells of stomach from producing acid (omeprezole, lansoprezole). Yet another form of drug therapy includes motility drugs for quickening the emptying of stomach contents (cisipride, bethanechol and metclopramide). The above-described drug therapies will reduce acid reflux thus reducing pain to the patient, but either have no impact on, or even increase alkaline reflux which can cause severe erosions in the esophagus. Further, there exists increasing evidence that lifetime drug therapies can result in atrophic gastritis in certain patients, which is known precursor to Barrett""s esophagus.
Since GERD is caused by an anatomic (mechanical) defect, certain surgeries are well suited to correct the defect by effectively lengthening the LES and/or increasing intraluminal pressures within the LES to prevent acid reflux. The leading surgical procedure is a endoscopic Nissen fundoplication, in which the surgeon develops a fold (plication) in the fundus of the stomach and then wraps and sutures the plication generally around the LES to increase intra-esophageal pressures therein. An endoscopic Nissen fundoplication is difficult to perform and typically requires the use of several disposable surgical instruments that are expensive. An open surgery to accomplish a Nissen fundoplication also is possible but undesirable because it requires lengthy postoperative recuperation and results in a long disfiguring upper abdominal incision.
There is therefore a need for a new therapies for treating GERD that offer mechanical or biomechanical solutions to the anatomic defect that underlies gastro-esophageal reflux. Preferably, such new approaches to alleviate acid reflux will not rely on lifetime drug therapies which do not correct the anatomic defect causing acid reflux.
The principal objects of this invention are to provide instruments and techniques for least invasive delivery of thermal energy through a tissue surface to a targeted tissue volume to accomplish the controlled remodeling of the treated tissue, and may also be referred to as bulking tissue. The targeted tissues that can be treated in a xe2x80x9cleast invasivexe2x80x9d manner include, but not limited to, soft tissues in the interior of a body (in particular, collagenous tissues such as fascia, ligamentous tissue), collagen-containing walls of vessels and organs, and anatomic structures having, supporting or containing an anatomic lumen (e.g., esophagus, urethra). Such tissues hereafter may be referred to as xe2x80x9ctargetedxe2x80x9d tissue volumes or xe2x80x9ctarget sitesxe2x80x9d.
More particularly, the invention discloses techniques and instruments that utilize radiofrequency (Rf) energy delivery to selectively injure cells and extracellular compositions (e.g., proteins) in a target site to induce a biological response to the injuryxe2x80x94such biological response including cell reproduction to an extent but more importantly the population of the extracellular space with collagen fibers in a repair matrix. Thus, the controlled alteration or modeling of the structural and mechanical characteristics of a targeted tissue site is possible by synthesis of new collagen fibers (or xe2x80x9cbulking effectsxe2x80x9d) therein. The above-described objects of the invention are enhanced by controlled manipulation of certain bio-physical characteristics of the target tissue prior to the delivery of Rf energy to induce the injury healing process. Besides the synthesis of collagen matrices, another object of the invention is the acute shrinkage of native collagen fibers in the targeted tissue volume. Such acute collagen shrinkage can cause tightening of a targeted tissue volume.
The injury healing process in a human body is complex and involves an initial inflammatory response which in collagenous tissues is followed by a subsequent response resulting in the population of new (nascent) collagen in the extracellular space. A mild injury may produce only an inflammatory reaction. More extensive tissue trauma invokes what is herein termed the injury healing response. Any injury to tissue, no matter whether mechanical, chemical or thermal may induce the injury healing response and cause the release of intracellular compounds into the extracellular compartment of the injury site. This disclosure relates principally to induction of the injury healing process by a thermally-mediated therapy. The temperature required to induce the response ranges from about 40xc2x0 C. to 70xc2x0 C. depending on the targeted tissue and the duration of exposure. Such a temperature herein may be referred to as Tncs (temperature that causes xe2x80x9cnew collagen synthesisxe2x80x9d). The temperature needed to cause such injury and collagen synthesis is lower than the temperature Tsc (temperature for acute xe2x80x9cshrinkage of collagenxe2x80x9d) in another modality of the method of the invention disclosed herein.
In order to selectively injure a target tissue volume to induce the population of the extracellular compartment with a collagen matrix, xe2x80x9ccontrolxe2x80x9d of the injury to a particular tissue is required. In this disclosure, a Rf energy source is provided to selectively induce the injury healing process. (It should be appreciated that other thermal energy devices are possible, for example a laser). In utilizing an Rf energy source, a high frequency alternating current (e.g., from 100,000 Hz to 500,000 Hz) is adapted to flow from one or more electrodes into the target tissue. The alternating current causes ionic agitation and friction in the targeted tissue as the ions follow the changes in direction of the alternating current. Such ionic agitation or frictional heating thus does not result from direct tissue contact with a heated electrode.
In the delivery of energy to a soft tissue volume, I=E/R where I is the intensity of the current in amperes, E is the energy potential measured in volts and R is the tissue resistance measured in ohms. In such a soft tissue volume, xe2x80x9ccurrent densityxe2x80x9d or level of current intensity is an important gauge of energy delivery which relates to the impedance of the tissue volume. The temperature level generated in the targeted tissue volume thus is influenced by several factors, such as (i) Rf current intensity (ii) Rf current frequency, (iii) tissue impedance levels within the targeted tissue volume, (v) heat dissipation from the targeted tissue volume, (vi) duration of Rf delivery, and (vii) distance of the targeted tissue volume from the electrodes. A subject of the present invention is the delivery of xe2x80x9ccontrolledxe2x80x9d thermal energy to a targeted tissue volume with a computer controlled system to vary the duration of current intensity and frequency together, based on sensor feedback systems.
In the initial cellular phase of injury healing, granulocytes and macrophages appear and remove dead cells and debris. In the inflammation process, the inflammatory exudate contains fibrinogen which together with enzymes released from blood and tissue cells, cause fibrin to be formed and laid down in the area of the tissue injury. The fibrin serves as a hemostatic barrier and thereafter acts as a scaffold for repair of the injury site. Fibroblasts migrate and either utilize the fibrin as scaffolding or for contact guidance thus further developing a fiber-like scaffold in the injury area. The fibroblasts not only migrate to the injury site but also proliferate. During this fibroplastic phase of cellular level repair, a extracellular repair matrix is laid down that is largely comprised of collagen. Depending on the extent of the injury to tissue, it is the fibroblasts that synthesize the collagen within the extracellular compartment as a form of connective tissue (hereafter nascent collagen), typically commencing about 36 to 72 hours after the injury.
Thus, in the injury healing response, compound tissues or organs are repaired by such fibrous connective tissue formation (or matrix formation). Such fibrous connective tissue is the single most prevalent tissue in the body and gives structural rigidity or support to tissues masses or layers. The principal components of such connective tissues are three fiber-like proteinsxe2x80x94collagen, reticulin and elastin along with a ground substrate. The bio-mechanical properties of fibrous connective tissue and the repair matrix are related primarily to the fibrous proteins of collagen and elastin. As much as 25% of total body protein is native collagen. In repair matrix tissue, it is believed that nascent collagen is in excess of 50%.
The unique properties of collagen are well known. Collagen is an extracellular protein found in connective tissues throughout the body and thus contributes to the strength of the musculo-skeletal system as well as the structural support of organs. Numerous types of collagen have been identified that seem to be specific to certain tissues, each differing in the sequencing of amino acids in the collagen molecule.
It has been previously recognized that collagen (or collagen fibers as later defined herein) will shrink or contract longitudinally when elevated in temperature to the range of 60xc2x0 C. to 80xc2x0 C., herein referred to as Tsc. Portions of this disclosure relate to techniques for controlled shrinkage of collagen fibers in the soft tissue, and more generally to the contraction of a collagen-containing tissue volume, (including both native collagen and nascent collagen) for therapeutic purposes.
Collagen consists of a continuous helical molecule made up of three polypeptide coil chains. Each of the three chains is approximate equal length with the molecule being about 1.4 nanometers in diameter and 300 nm. in length along its longitudinal axis in its helical domain domain (medial portion of the molecule). The spatial arrangement of the three peptide chains in unique to collagen with each chain existing as a right-handed helical coil. The superstructure of the molecule is represented by the three chains being twisted into a left-handed superhelix. The helical structure of each collagen molecule is bonded to together by heat labile intermolecular cross-links (or hydrogen cross-links) between the three peptide chains providing the molecule with unique physical properties, including high tensile strength along with moderate elasticity. Additionally, there exist heat stabile or covalent cross-links between the individual coils. The heat labile cross-links may be broken by mild thermal effects thus causing the helical structure of the molecule to be destroyed with the peptide chains separating into individual randomly coiled structures. Such thermal destruction of the cross-links results in the shrinkage of the collagen molecule along its longitudinal axis to up to one-third of its original dimension, in the absence of tension.
A plurality of collagen molecules (also called fibrils) aggregate naturally to form collagen fibers that collectively make up the a fibrous matrix. The collagen fibrils polymerize into chains in a head-to-tail arrangement generally with each adjacent chain overlapping another by about one-forth the length of the helical domain in a quarter stagger fashion to form a collagen fiber. Each collagen fiber reaches a natural maximum diameter, it is believed because the entire fiber is twisted resulting in an increased surface are that succeeding layers of fibrils cannot bond with underlying fibril in a quarter-stagger manner.
Thus, the present invention is directed to techniques and instruments for controlled thermal energy delivery to portions of a patient""s LES, in alternative therapies, either:
a) to selectively injury cells and proteins in walls of the LES to induce an injury healing response which populates the extracellular compartment with a collagen fiber matrix (xe2x80x9cnascent collagenxe2x80x9d) to bulk and alter the architecture and flexibility characteristics of tissue volumes within walls of the LES; or
b) to, optionally, shrink either xe2x80x9cnativexe2x80x9d collagen or xe2x80x9cnascentxe2x80x9d collagen in tissue volumes within the wall of the LES to further alter mechanical characteristics of the LES and increase intra-esophageal pressures.
More in particular, the device of the present invention for xe2x80x9cmodelingxe2x80x9d a collagen matrix in targeted tissue (or xe2x80x9cbulkingxe2x80x9d targeted tissue) in walls of the patient""s LES is fabricated as a flexible bougie that carries thermal energy delivery means in its distal working end. Typically an Rf source is connected to at least one electrode carried in the working end. The working end may carry a single electrode that is operated in a mono-polar mode or a plurality of electrodes operated in either a mono-polar or bi-polar manner, with optional multiplexing between various paired electrodes. A sensor array of individual sensors also is carried in the working end, typically including (i) thermocouples and control circuitry, and/or (ii) impedance-measuring circuitry coupled to the electrode array.
A computer controller is provided, together with the feedback circuitry from the sensor systems, that is capable of full process monitoring and control of: (i) power delivery, (ii) parameters of a selected therapeutic cycle, (iii) mono-polar or bi-polar energy delivery, and (iv) multiplexing Rf delivery. The controller also can determine when the treatment is completed based on time, temperature, tissue impedance or any combination thereof.
In a first method of the invention, the device is introduced through the patient""s mouth until the working end and electrode array is positioned within the LES. The therapeutic phase commences and is accomplished under various monitoring mechanisms, including but not limited to (i) direct visualization, (ii) measurement of tissue impedance of the target tissue masses relative to the device, and (iii) utilization of ultrasound imaging before or during treatment. The physician actuates the pre-programmed therapeutic cycle for a period of time necessary to elevate the target tissue mass to Tncs (temperature of new collagen synthesis) which is from 45xc2x0 to 60xc2x0 depending on duration of energy delivery.
During the therapeutic cycle, the delivery of thermal energy is conducted under full-process feedback control. The delivery of thermal energy induces the injury healing response which thereafter populates the mass with an extracellular collagen matrix and reduces the flexibility of the LES over the subsequent several days and weeks. The physician thereafter may repeat the treatment.
In a second method of the invention, (either the initial or a subsequent therapeutic cycle) the delivery of Rf energy may be elevated to shrink collagen fibers at a range between 60xc2x0 to 80xc2x0 C. to reach Tsc. The effect of such collagen shrinkage is to rigidify or bulk the treated tissue volumes in the wall of the LES.
Following an initial therapeutic cycle, the treatment can be repeated until the desired increase in intra-esophageal pressures is achieved. It is believed that such periodic treatments (e.g., from 2 to 6 treatments over a period of several weeks) may be best suited to treat the LES.
The above-described modalities of (i) induced synthesis of collagen in collagenous tissues, and (ii) shrinkage of collagen in collagenous tissues describe the effects on LES tissue volumes. These methods of treating the LES are defined herein by a particular temperature range that causes the exact cellular/extracellular effects in the targeted tissue volumes, and are intended to be inclusive of other descriptive terms that may be used to more generally characterize treatments, such as tightening tissue, bulking tissue, fusing or fusion of collagenous tissues, creating scar tissue, sealing or welding collagen-containing tissue, shrinking tissue and the like. The methods disclosed herein are not defined to include ablating tissue, which occurs at higher temperature levels.
In general, the present invention advantageously provides least invasive thermally-mediated techniques for increasing intraluminal pressures in a patient""s LES to prevent gastro-esophageal reflux.
The present invention provides novel devices and techniques for thermally inducing an injury healing response to alter cellular/extracellular architecture in the LES.
The present invention provides techniques for thermal induction of bulking of tissue volumes around a sphincter in an anatomic lumen.
The present invention advantageously provides an electrode array for delivering a controlled amount of Rf energy to a specific targeted tissue volume in the LES having a particular shape or pattern.
The present invention provides an electrode array for delivering a controlled amount of Rf energy to a specific target collagen-containing tissue volume to achieve a controlled contraction of the collagen fibers therein.
The present invention provides a novel device and technique for contraction of collagen fibers around the lumen of an anatomic structure to reduce the dimension of the lumen.
The present invention also provides an instrument and method in which a bougie-type member has a working channel to accommodate an endoscope, an accessory instrument or for therapeutic agent delivery or suction.
The present invention advantageously provides a device that is inexpensive and disposable.
Additional advantages and features of the invention appear in the following description in which several embodiments are set forth.